Diminished differentiation of rewards in individuals at clinical high-risk for psychosis.

Reward processing is impaired in people with schizophrenia, which may begin in the clinical high-risk (CHR) for psychosis period. The Monetary Incentive Delay (MID) task has been important in understanding the neural correlates of reward processing deficits in various psychiatric disorders. Previous research has found that CHR individuals have an imprecise mental representation of rewards, which leads to a diminished differentiation between rewards, though this has not been observed behaviorally. A total of 19 CHR individuals and 20 controls were given a novel variant of the MID task, designed to examine how modulating reward context may impact responses to reward cues, a process often referred to as "adaptive coding." Both groups appeared to update their behavior in response to the rewards available in this adaptive task. However, when compared to controls who showed a more graded decrease in response time to increasing reward contexts, CHR individuals appeared to have a sharp decrease in response time in the low reward context that is nearly stable across higher reward contexts. This is largely driven by the exponential component of the response time distribution, which is often interpreted to be more cognitively or effortfully influenced. Response times are related to negative symptoms, but not positive symptoms, disorganized symptoms, or estimated intelligence. Although an adaptive coding effect was not observed, these results provide novel insight into the reward processing mechanisms and volitional processes in the CHR population, as this was the first study to observe the diminished differentiation of rewards behaviorally.

Mechanism unravelling for highly efficient and selective 99TcO4 - sequestration utilising crown ether based solvent system from nuclear liquid waste: experimental and computational investigations.

Selective and efficient separation of pertechnetate (TcO4 -) from nuclear waste is desirable for the safe and secure management of radioactive waste. Here, we have projected dibenzo-18-crown-6 ether (DB18C6) in a highly polar nitrobenzene medium for enhancing the removal efficiency of 99Tc from reprocessing plant low level waste (LLW). An effort was made to determine the stoichiometry of metal-ligand complex by slope ratio method, revealing that one ligand (DB18C6) binds with one TcO4 - moiety. Optimum ligand concentration for 99Tc extraction was evaluated. Relevant interference of the anions was studied systematically. The effect of solution pH was analysed on the extraction efficiency of 99Tc. A kinetic study was carried out for maximum extraction of metal ions. A quantitative stripping study was also achieved for metal ions with a suitable stripping solution. After evaluation of all essential parameters, selectivity and feasibility studies were finally carried out with actual low level reprocessing plant waste to demonstrate a laboratory scale process for effective separation of TcO4 - ions. Density functional theory (DFT) calculations were carried out to understand the nature of the complexation of TcO4 - ion with DB18C6 in different solvents systems and to elucidate the key aspect behind ionic selectivity and enhanced the 99Tc extraction efficiency of DB18C6 in the studied diluent systems. The ΔE and ΔG values for different modeled complexation reactions were evaluated systematically. From the calculated free energy of complexation of TcO4 - with DB18C6, it was observed that the consideration of explicit solvent plays a vital role in predicting the experimental selectivity.

Correction: Mechanism unravelling for highly efficient and selective 99TcO4 - sequestration utilising crown ether based solvent system from nuclear liquid waste: experimental and computational investigations.

[This corrects the article DOI: 10.1039/D1RA07738D.].

The Critical Roles of Early Development, Stress, and Environment in the Course of Psychosis.

Psychotic disorders are highly debilitating with poor prognoses and courses of chronic illness. In recent decades, conceptual models have shaped understanding, informed treatment, and guided research questions. However, these models have classically focused on the adolescent and early adulthood stages immediately preceding onset while conceptualizing early infancy through all of childhood as a unitary premorbid period. In addition, models have paid limited attention to differential effects of types of stress; contextual factors such as local, regional, and country-level characteristics or sociocultural contexts; and the timing of the stressor or environmental risk. This review discusses emerging research suggesting that (a) considering effects specific to neurodevelopmental stages prior to adolescence is highly informative, (b) understanding specific stressors and levels of environmental exposures (i.e., systemic or contextual features) is necessary, and (c) exploring the dynamic interplay between development, levels and types of stressors, and environments can shed new light, informing a specified neurodevelopmental and multifaceted diathesis-stress model.

Testing whether implicit emotion regulation mediates the association between discrimination and symptoms of psychopathology in late childhood: An RDoC perspective.

Discrimination has been associated with adverse mental health outcomes, though it is unclear how early in life this association becomes apparent. Implicit emotion regulation, developing during childhood, is a foundational skill tied to a range of outcomes. Implicit emotion regulation has yet to be tested as an associated process for mental illness symptoms that can often emerge during this sensitive developmental period. Youth aged 9-11 were recruited for the Adolescent Brain Cognitive Development (ABCD) study. Associations between psychotic-like experiences, depressive symptoms, and total discrimination (due to race, ethnicity, nationality, weight, or sexual minority status) were tested, as well as associations with implicit emotion regulation measures (emotional updating working memory and inhibitory control). Analyses examined whether associations with symptoms were mediated by implicit emotion regulation. Discrimination related to decreased implicit emotion regulation performance, and increased endorsement of depressive symptoms and psychotic-like experiences. Emotional updating working memory performance partially mediated the association between discrimination and psychotic-like experiences, while emotional inhibitory control did not. Discrimination and implicit emotion regulation could serve as putative transdiagnostic markers of vulnerability. Results support the utility of using multiple units of analysis to improve understanding of complex emerging neurocognitive functions and developmentally sensitive periods.

Using search engine data to gauge public interest in mental health, politics and violence in the context of mass shootings.

Despite significant potential for providing insight to private perceptions and behaviors, search engine data has yet to be utilized as a means of gauging the U.S. public's interest and understanding of mental health in the context of gun violence and politics. An analysis of Google Trends revealed that Mental health searches increased in volume starting in the beginning of the current decade. Notably, both "mental health" and "gun(s)" were searched with greater frequency the week after the mass shooting events occurred. Related searches after the event also observed a significant increase in interest in mental health and gun regulation, legal reform, mass shootings, and gun(s). Results suggest that the American public's perception of mental illness increasingly incorporates associations with themes of violence and politics, which becomes more apparent surrounding mass shooting events. Future studies are needed to determine implications for stigmatization of vulnerable groups, and possible relations to media coverage.

Comparison of Healthcare Resource Utilization and Costs between Rivaroxaban and Warfarin for Nonvalvular Atrial Fibrillation in a Skilled Nursing Facility Setting.

BACKGROUND: Use of direct-acting oral anticoagulants for patients with nonvalvular atrial fibrillation (NVAF) in skilled nursing facilities (SNFs) is increasing. Rivaroxaban is commonly used in this setting as an alternative to warfarin, based on comparable or increased efficacy in preventing stroke and a similar or lower risk of major bleeding. OBJECTIVE: The aim of this study was to compare healthcare resource utilization (HCRU) and costs between NVAF patients receiving rivaroxaban or warfarin in SNFs. METHODS: This retrospective study examined de-identified claims from Optum® Clinformatics® Extended Data Mart (1 January 2013-31 December 2017). Eligible patients had an AF diagnosis, were prescribed rivaroxaban or warfarin during an SNF stay, and had one or more such prescriptions filled in the 6 months preceding the stay. Patients were excluded if they received another oral anticoagulant or had evidence of valvular heart disease, mitral stenosis, or organ/tissue transplant. HCRU, mean number of events, and all-cause healthcare costs during the index SNF stay were reported. Results were also reported on a per-patient-per-month (PPPM) basis. Exploratory analyses at different time periods were also conducted. RESULTS: Overall, 4423 rivaroxaban patients and 22,796 warfarin patients were identified prior to inverse probability of treatment weighting adjustment. Index SNF stay was significantly shorter among rivaroxaban-treated patients (35.8 ± 35.8 days) versus warfarin (40.1 ± 46.3 days; p < 0.0001). During the SNF stay, overall HCRU was lower for the rivaroxaban cohort versus the warfarin cohort. All-cause total costs were significantly reduced for rivaroxaban ($6450 ± $10,379) versus warfarin ($7640 ± $16,556; p < 0.0001), and similar results were observed when calculated on a PPPM basis. During the 1-year post-index period, PPPM all-cause total costs were significantly lower with rivaroxaban versus warfarin ($4135 vs. $4561; p < 0.0001). CONCLUSION: In this SNF setting, HCRU and costs were lower among patients with NVAF who were experienced users of rivaroxaban compared with those who were experienced users of warfarin. These findings may help inform clinical decision making to reduce the economic burden of NVAF among older adults in SNFs.

Healthcare resource utilization and costs among nonvalvular atrial fibrillation patients initiating rivaroxaban or warfarin in skilled nursing facilities: a retrospective cohort study.

Objective: Atrial fibrillation (AF) is present in up to 17% of patients in skilled nursing facilities (SNFs). This study compared healthcare resource utilization (HRU) and costs between AF patients initiating rivaroxaban or warfarin in SNFs.Methods: Using de-identified claims from Optum Clinformatics Extended Data Mart (1 January 2013 to 31 December 2017), this retrospective cohort study indexed AF patients with first SNF admission during which rivaroxaban or warfarin was initiated within 3 days of admission. To adjust for selection bias, inverse probability of treatment weighting (IPTW) was applied for baseline characteristics. Logistic regression and generalized linear models were used to compare HRU and costs.Results: 519 rivaroxaban and 1129 warfarin patients met inclusion criteria. After IPTW, the cohorts were well balanced for baseline characteristics. The average length of index SNF stay was 32.07 and 37.44 days for rivaroxaban and warfarin patients, respectively. During SNF stay, rivaroxaban patients had 27% lower odds of hospitalization (p < .0001), 2.7 fewer international normalized ratio (INR) tests per-patient-per-month (PPPM; p < .001), and 2.3 fewer pathology/laboratory encounters PPPM (p < .0001) than warfarin patients. All-cause healthcare costs were $2638 lower with rivaroxaban versus warfarin (p < .0001) during the index SNF stay, with lower medical costs (p < .0001) but higher pharmacy costs (p < .0001). Total all-cause healthcare costs 100 days post-index SNF were $8746 lower with rivaroxaban versus warfarin (p < .0001).Conclusions: In the SNF setting, AF patients treated with rivaroxaban had 5-day shorter length of stay, lower HRU, and lower all-cause total and medical costs compared to warfarin, despite higher treatment costs. These findings may help inform clinical decision-making to reduce economic burden.

The utility of an RDoC motor domain to understand psychomotor symptoms in depression.

Despite the clinical impact of motor symptoms such as agitation or retardation on the course of depression, these symptoms are poorly understood. Novel developments in the field of instrumentation and mobile devices allow for dimensional and continuous recording of motor behavior in various settings, particularly outside the laboratory. Likewise, the use of novel assessments enables to combine multimodal neuroimaging with behavioral measures in order to investigate the neural correlates of motor dysfunction in depression. The research domain criteria (RDoC) framework will soon include a motor domain that will provide a framework for studying motor dysfunction in mood disorders. In addition, new studies within this framework will allow investigators to study motor symptoms across different stages of depression as well as other psychiatric diagnoses. Finally, the introduction of the RDoC motor domain will help test how motor symptoms integrate with the original five RDoC domains (negative valence, positive valence, cognitive, social processes, and arousal/regulation).

Enhancement of bulk second-harmonic generation from silicon nitride films by material composition.

We present a comprehensive tensorial characterization of second-harmonic generation from silicon nitride films with varying compositions. The samples were fabricated using plasma-enhanced chemical vapor deposition, and the material composition was varied by the reactive gas mixture in the process. We found a six-fold enhancement between the lowest and highest second-order susceptibility, with the highest value of approximately 5 pm/V from the most silicon-rich sample. Moreover, the optical losses were found to be sufficiently small (below 6 dB/cm) for applications. The tensorial results show that all samples retain in-plane isotropy independent of the silicon content, highlighting the controllability of the fabrication process.

Reactivity to uncertain threat as a familial vulnerability factor for alcohol use disorder.

BACKGROUND: When sober, problematic drinkers display exaggerated reactivity to threats that are uncertain (U-threat). Since this aversive affective state can be alleviated via acute alcohol intoxication, it has been posited that individuals who exhibit heightened reactivity to U-threat at baseline are motivated to use alcohol as a means of avoidance-based coping, setting the stage for excessive drinking. To date, however, no study has attempted to characterize the dispositional nature of exaggerated reactivity to U-threat and test whether it is a vulnerability factor or exclusively a disease marker of problematic alcohol use. METHOD: The current investigation utilized a family study design to address these gaps by examining whether (1) reactivity to U-threat is associated with risk for problematic alcohol use, defined by family history of alcohol use disorder (AUD) and (2) reactivity to U-threat is correlated amongst adult biological siblings. A total of 157 families, and 458 individuals, participated in the study and two biological siblings completed a threat-of-shock task designed to probe reactivity to U-threat and predictable threat (P-threat). Startle potentiation was collected as an index of aversive responding. RESULTS: Within biological siblings, startle potentiation to U-threat [intraclass correlation (ICC) = 0.35] and P-threat (ICC = 0.63) was significantly correlated. In addition, independent of an individuals' own AUD status, startle potentiation to U-threat, but not P-threat, was positively associated with risk for AUD (i.e. AUD family history). CONCLUSION: This suggests that heightened reactivity to U-threat may be a familial vulnerability factor for problematic drinking and a novel prevention target for AUD.

Molecular epidemiology of Crimean-Congo haemorrhagic fever virus in India.

Crimean-Congo haemorrhagic fever (CCHF) is an emerging zoonotic disease in India which is prevalent in neighbouring countries. CCHF virus (CCHFV) is a widespread tick-borne virus which is endemic in Africa, Asia, Eastern Europe and the Middle East. In the present study, samples of clinically suspected human cases from different areas of northern-western India were tested for the presence of CCHFV by RT-PCR through amplification of nucleocapsid (N) gene of CCHFV. Positive samples were sequenced to reveal the prevailing CCHFV genotype(s) and phylogenetic relatedness. A phylogenetic tree revealed the emergence of diverse strains in the study region showing maximum identity with the Pakistan, Afghanistan and Iran strains, which was different from earlier reported Indian strains. Our findings reveal for the first time the emergence of the Asia 1 group in India; while earlier reported CCHFV strains belong to the Asia 2 group.

Thirty-day readmissions after inpatient laparoscopic cholecystectomy: factors and outcomes.

BACKGROUND: 30-day readmissions are a considerable financial burden on medical institutions due to penalties faced from the Centers for Medicaid and Medicare. METHODS: A retrospective review of 30-day readmissions was performed. The data were subdivided into medical severity-diagnostic related groups 417, 418, and 419, as categorized by the Centers for Medicaid and Medicare. Perioperative variables, diagnostic workup, operative interventions, and postoperative morbidity and outcomes were analyzed. RESULTS: Forty-four (5.9%) readmissions were recorded, of 747 inpatient discharges. The data were further divided into DRGs 417, 418, and 419 with readmission rates of 13.6, 3.6%, and 5.4%, respectively. The highest rate of readmission was within the first 7 days. Etiology was divided into surgical (54.5%) and nonsurgical (45.4%). CONCLUSIONS: Patients with major comorbidities had a higher rate of readmission (P < .05). In 45.4% of the readmissions, the cause was found to be nonsurgical. The surgical team was not consulted in 31.8% of the readmissions.

Iron binding to caseins in the presence of orthophosphate.

As adding >5mM ferric chloride to sodium caseinate solutions results in protein precipitation, the effects of orthophosphate (0-64 mM) addition to sodium caseinate solution (2% w/v protein) on iron-induced aggregation of the caseins were studied at pH 6.8. Up to 20mM ferric chloride could be added to sodium caseinate solution containing 32 mM orthophosphate without any protein precipitation. The addition of iron to sodium caseinate solution containing orthophosphate reduced the diffusible phosphorus content in a concentration-dependent manner. Added iron appeared to interact simultaneously with phosphoserine on the caseins and inorganic phosphorus. The relative sizes of the casein aggregates were governed by the concentration of orthophosphate and the aggregates consisted of all casein fractions, even at the lowest level of ferric chloride addition (5mM). It is hypothesised that the addition of iron to caseins in the presence of orthophosphate results in the formation of colloidal structures involving casein-iron-orthophosphate interactions.

Predictors for the need of surgery in antenatally detected hydronephrosis due to UPJ obstruction--a prospective multivariate analysis.

INTRODUCTION: Disagreement exists over the ability of different diagnostic tests to define obstruction, indications and timing of surgery and which patients will benefit from surgical intervention in antenatal hydronephrosis (ANH) due to ureteropelvic junction obstruction (UPJO). We try to find a way to predict which patients of ANH due to UPJO will eventually need surgery during conservative management. MATERIAL AND METHODS: Prospective single centre study involving 122 renal units at a referral centre in India. Patients on conservative management were followed using a standard protocol and operated for pre-defined indications defining failure of conservative management. Patients who underwent surgery were compared with the non-operated group in terms of sex, side, baseline grade of hydronephrosis, maximum anterioposterior diameter on first postnatal ultrasound and differential renal function on first renal scan. RESULTS: A total of 109 renal units qualified for conservative management. Of those, 23.9% required operative intervention during follow-up. Median time to failure of conservative management was 37 weeks. The median follow-up of non-operated cases was 54 months. Univariate analysis revealed that society of fetal urology (SFU) grade of hydronephrosis, anteroposterior diameter (APD), cortical thickness (CT), and pre-operative differential renal function (DRF) had a significant association with surgery (P < 0.05). Multivariate analysis revealed APD and pre-operative DRF as the only independent predictors for requiring surgery, while CT and initial SFU grade of hydronephrosis were not. Receiver operating curve analysis showed that an APD of 24.3 mm could predict the need for surgery, with a sensitivity of 73.1% and a specificity of 88.0%. CONCLUSIONS: APD and DRF are the predictive factors for surgery. We stop short of recommending surgery only on the basis of APD. Instead we recommend that efforts be made to improve the specificity of this criterion, or by using APD in perspective with the differential renal function. We can reduce the burden of investigations in those with APD <24 mm while those with APD >24 mm can be more comprehensively monitored.

Updating the research domain criteria: the utility of a motor dimension.

Within the NIMH Research Domain Criteria (RDoC) framework, dimensions of behavior are investigated across diagnoses with the goal of developing a better understanding of their underlying neural substrates. Currently, this framework includes five domains: cognitive, social, arousal/regulatory, negative, and positive valence systems. We argue that the inclusion of a motor systems domain is sorely needed as well. Independent of medication, distinct areas of motor dysfunction (e.g. motor planning/inhibition/learning/coordination, involuntary movements) commonly appear across a number of mental disorders (e.g. schizophrenia, bipolar disorder, autism, attention deficit hyperactivity disorder, Alzheimer's disease, depression) as well as neurological disorders accompanied by significant psychological symptoms (e.g. Parkinson's disease). In addition, motor systems are amenable to study across multiple levels of analysis from the cellular molecular level focusing on cytoarchitechtonics and neurotransmitter systems, to networks and circuits measured using neuroimaging, and finally at the level of overt behavioral performance. Critically, the neural systems associated with motor performance have been relatively well defined, and different circuits have been linked to distinct aspects of motor behavior. As such, they may also be differentially associated with symptoms and motor dysfunction across diagnoses, and be uniquely informative about underlying etiology. Importantly, motor signs can change across stages of illness; they are also often present in the prodromal phases of disease and closely linked with course, suggesting that these behaviors represent a core feature reflective of pathogenic processes. The inclusion of a motor domain would allow researchers to better understand psychopathology more broadly, and may also reveal important contributions to disease processes across diagnoses.

Influence of calcium depletion on iron-binding properties of milk.

We investigated the effects of calcium depletion on the binding of iron in milk. A weakly acidic cation-exchange resin was used to remove 3 different levels (18-22, 50-55, and 68-72%) of calcium from milk. Five levels of iron (5, 10, 15, 20, and 25 mM) were added to each of these calcium-depleted milks (CDM) and the resultant milks were analyzed for particle size, microstructure, and the distribution of protein and minerals between the colloidal and soluble phases. The depletion of calcium affected the distribution of protein and minerals in normal milk. Iron added to normal milk and low-CDM (~20% calcium depletion) bound mainly to the colloidal phase (material sedimented at 100,000 × g for 1 h at 20 °C), with little effect on the integrity of the casein micelles. Depletion of ~70% of the calcium from milk resulted in almost complete disintegration of the casein micelles, as indicated by all the protein remaining in the soluble phase upon ultracentrifugation. Addition of up to ~20 mM iron to high CDM resulted in the formation of small fibrous structures that remained in the soluble phase of milk. It appeared that the iron bound to soluble (nonsedimentable) caseins in high-CDM. We observed a decrease in the aqueous phosphorus content of all milks upon iron addition, irrespective of their calcium content. We considered the interaction between aqueous phosphorus and added iron to be responsible for the high iron-binding capacity of the proteins in milk. The soluble protein-iron complexes formed in high-CDM (~70% calcium depletion) could be used as an effective iron fortificant for a range of food products because of their good solubility characteristics.